1. Field of the Invention
The invention relates to a compound, and in particular, to an isoxazole derivative for treatment of osteoporosis and cancer.
2. Description of the Related Art
The isoxazoles, especially 4,5-diarylisoxazole derivatives (the isoxazole skeleton bearing two neighboring aryl substituents), have been found to possess broad biological effects, including anti-inflammatory (Habeeb, A. G. et. al. J. Med. Chem. 2001, 44, 2921; Habeeb, A. G. et. al. Drug Dev. Res. 2000, 51, 273; Talley, J. J. Patent No. US 1999/U.S. Pat. No. 5,859,257) and anticancer activities (Zhang, Q. et. al. J. Med. Chem. 2007, 50, 749; Sun, C. M. et. al. Bioorg. Med. Chem. Lett. 2007, 17, 1078; Peifer, C. et. al. J. Med. Chem. 2006, 49, 1271; Kaffy, J. et. al. Bioorg. Med. Chem. 2006, 14, 4067; Sanchez Maya, A. B. et. al. Bioorg. Med. Chem. 2005, 13, 2097).
Recently, certain structural analogues of 4,5-diarylisoxazole derivatives have been extensively explored as potential anticancer agents. For example, the cytotoxic combretastatin A-4 (Liou, J. P. et. al. J. Med. Chem. 2004, 47, 4247; Petit, G. R. et. al. Can. J. Chem. 1982, 60, 1374; Lin, C. M. et. al. Mol. Pharmacol. 1988, 34, 200) can be considered as an analogue of 4,5-diarylisoxazole in which the isoxazole moiety is replaced with a simple ethylene bridge. Other 4,5-diarylisoxazole analogues, such as the replacement of isoxazole moiety with a cyclopentene ring (Gurjar, M. K. et. al. J. Med. Chem. 2007, 50, 1744) or a five membered heterocyclic ring (Pirali, T. et. al. J. Med. Chem. 2006, 49, 5372; Tron, G. C. et. al. J. Med. Chem. 2006, 49, 3033), have also been synthesized and evaluated for their anticancer activities. Therefore, structural optimization of 4,5-diarylisoxazole has led to the discovery of potential drug candidates. Researchers are interested in the investigation of 4,5-diarylisoxazole derivatives as anti-osteoporotic agents because certain 4,5-diarylisoxazole analogues, in which the isoxazole moiety is replaced with a pyrazolopyrimidine ring (Zhou, H. B. et. al. J. Med. Chem. 2007, 50, 399; Compton, D. R. et. al. Bioorg. Med. Chem. 2004, 14, 5681; Compton, D. R. et. al. J. Med. Chem. 2004, 47, 5872), have been discovered to possess estrogen receptor beta antagonist activity.
Ipriflavone (Kunikata, K. et. al. Patent No. JP 1996/09268187 A; Imamiya, K. et. al. Patent No. JP 1997/11012265 A; Yamazaki, I. et. al. Patent No. EP 1984/136569 A2; Ferrari, M. Patent No. EP 1999/941992 A1; Ferrari, M. Patent No. EP 2002/941992 B1), one of the synthetic isoflavone derivatives, has been approved for the treatment of involutional osteoporosis in some European countries and in Japan.